Malaria is a global problem affecting over 200 million people each year. It is the cause of approximately four million deaths annually, mostly children, in developing countries. Although it was common in the southern states before World War II, malaria has been effectively eliminated in the United States. It now occurs most often in tropical and subtropical countries and also in temperate regions during the summer months. The disease is most prevalent in Africa, Southeast Asia and Latin America. However, malaria is not just a problem for the developing countries in which it occurs. It is an impediment to world development as it affects tourism and trade.
Human malaria can be caused by one of four known parasites: Plasmodium ovale, Plasmodium malariae, Plasmodium vivax, and Plasmodium falciparum. Although Plasmodium vivax is the most common cause of the disease, Plasmodium falciparum causes the most deadly form. Plasmodium falciparum is transmitted by the saliva of an infected female Anopheles mosquito. When an Anopheles mosquito bites a patient with malaria it sucks up blood cells containing malaria parasites. The parasites develop and multiply in the mosquito's stomach and them move into its salivary glands. When the malaria-infected mosquito infects sporozoites in its saliva, they migrate first to the liver where they replicate in hepatocytes, then they migrate through the bloodstream and infect red blood cells. This is called the liver-stage and is responsible for recurrent infections. When the mosquito bites again, it injects saliva containing the parasites. The parasites enter the victims red blood cells, complete their life cycle and then burst the blood cell causing the characteristic anemia and fever as the body tries to fight the foreign invasion. Infected individuals initially suffer from aches, fever, nausea and often vomiting. Symptoms of mild cases include drenching sweats and shaking chills, followed by months or even years of anemia and periodic fevers. Children infected with a P. falciparum can die within a few days after the first symptoms as ravaged blood cells clog capillaries and deprive the brain of oxygen.
Several approaches have been used in attempting to control the spread of malaria. One approach is to eliminate mosquito reproduction by draining the swamps and marshes where they reproduce or spraying the breeding grounds with oil or chemicals that destroy the larvae. However, draining or spraying disease infested swamps and marshes is impractical in many parts of the world and finding every swamp and marsh is impossible.
Much effort has focused on developing effective methods for killing the infected adult mosquitoes with insecticides. Studies of the habits of mosquitoes have shown that many types of mosquitoes bite only when they are indoors at night. Immediately after biting, they seek rest on a nearby surface. Spraying the walls and ceilings of indoor rooms with insecticides such as DDT and dieldrin, which remain active for a long time, has been somewhat effective in reducing the incidence of malaria. However, it is clear that mosquitoes are developing resistance to the pesticides being used.
Defense forces from Australia, the U.S. and Canada have tested clothes which have been treated with the insecticide Perigen to protect the wearer from mosquitoes or other insects that feed on blood. Although undergarments may be worn to protect the skin from the insecticide on the clothes, it is thought that the long term effects of the pesticide so close to the human body may be worse than the risks of malaria. In addition, there remains the growing problem of mosquito resistance to insecticides.
Another approach to preventing the spread of malaria is the use of chemotherapy drugs to kill the parasite in a patient. Many different drugs have been used to prevent and/or treat malaria, including quinine, atabrine, chloroquine, mefloquine, and primaquine. The drugs work in the patient by killing the parasite at various stages of its life cycle. However, parasite resistance to some drugs is an increasingly serious problem. Resistance is often due to mutation of the parasites' proteins. Researchers at John Radcliffe Hospital in Headington, England, have found the mutation rate in P. falciparum, for example, is 2% per generation. Mutation of surface proteins may help the parasites avoid the immune system of their victims and makes it difficult to develop vaccines. Scientists predict that since malaria parasites are becoming resistant to all known drugs, malaria may be untreatable in the near future.
There are serious drawbacks to the use of many existing anti-malaria drugs because of the side effects they produce in patients. For example, chloroquine can cause gastrointestinal disturbances, visual disturbances, irreversible damage to the retina, skin reactions, hair loss and hair depigmentation. Furthermore, chloroquine must be used with caution, if at all, in patients with hepatic and renal impairment and may be contra-indicated in patients with psoriasis, epilepsy and other neurological conditions.
Another drug with serious side effects is Artemether (Paluther) which is used for the treatment of acute outbreaks of quinine resistant malaria. Artemether is based on a semi-synthetic derivative of an ancient Chinese herbal pharmaceutical and has the severe drawback of being associated with fatal neurotoxicity.
There may be hope for the use of antisense drugs that limit the growth of the parasite in patients, however research in this area has not progressed sufficiently for antisense drugs to be considered an imminent solution to the problem.
Scientists have predicted that global warming may bring an onslaught of diseases, such as malaria, the plague, yellow fever and others. The interrelated consequences of global warming, increased worldwide travel, and the current epidemic of drug resistant malaria parasites have created an urgent need for effective and safe drugs to treat and prevent the lethal or debilitating symptoms associated with the malaria parasite. The present invention satisfies this need and provides related advantages as well.